Muscella A, Greco S, Elia M G, Storelli C, Marsigliante S
Laboratorio di Fisiologia, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università di Lecce, Ecotekne, Via Prov. le per Monteroni, 73100 Lecce, Italy.
J Endocrinol. 2002 May;173(2):315-23. doi: 10.1677/joe.0.1730315.
Here we demonstrated, by RT-PCR analysis, the expression of both angiotensin II (Ang II) receptor subtypes, AT1 and AT2, in a breast cancer epithelial cell line, MCF-7. Ang II was not able to affect the intracellular Ca2+ concentration in Fura-2 loaded cells suggesting that AT1-mediated phospholipid hydrolysis is not involved in its intracellular transduction pathway. Ang II modulated the activity of the Na+/K+ATPase in a dose- and time-dependent manner and was mitogenic, with a dose-dependent (1-1000 nM) proliferative effect and a maximal response at 100 nM. Both Na+/K+ATPase activation and stimulation of proliferation were mediated by binding of Ang II to AT1, as the effects were completely blocked by DuP 753, a specific AT1 antagonist. CGP 42112, an AT2 antagonist, did not affect Ang II actions. The main conclusion of this study is that Ang II exerts its effects on cell proliferation and Na+/K+ATPase in breast cancer epithelial cells, MCF-7, via AT1 activation independently of the Ca(2+) signalling mechanism.
在此，我们通过逆转录聚合酶链反应（RT-PCR）分析证明，血管紧张素II（Ang II）的两种受体亚型AT1和AT2在乳腺癌上皮细胞系MCF-7中均有表达。Ang II无法影响负载Fura-2的细胞内Ca2+浓度，这表明AT1介导的磷脂水解不参与其细胞内转导途径。Ang II以剂量和时间依赖性方式调节Na+/K+ATP酶的活性，并且具有促有丝分裂作用，具有剂量依赖性（1-1000 nM）增殖效应，在100 nM时出现最大反应。Na+/K+ATP酶的激活和增殖刺激均由Ang II与AT1的结合介导，因为这些效应被特异性AT1拮抗剂DuP 753完全阻断。AT2拮抗剂CGP 42112不影响Ang II的作用。本研究的主要结论是，Ang II通过激活AT1对乳腺癌上皮细胞MCF-7中的细胞增殖和Na+/K+ATP酶发挥作用，而与Ca(2+)信号传导机制无关。
